Post Traumatic Stress Disorder
Conditions
Keywords
Traumatic Event, Trauma Survivor, Exposure Therapy, PTSD DCS, Virtual Reality Exposure, Veteran, Combat-related PTSD
Brief summary
The purpose of this study is to test the differences between four active treatment conditions for combat-related Post Traumatic Stress Disorder (PTSD): virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both with DCS or placebo, as well as to examine predictors for PTSD and response to treatment in active duty military personnel, veterans, and civilians who served in Iraq and Afghanistan.
Detailed description
Post Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop following exposure to traumatic events and includes symptoms of re-experiencing the trauma, such as through nightmares and flashbacks, avoidance and numbing, and physical hyperarousal. PTSD has been estimated to affect 10-20% of returning Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) veterans. The most effective intervention found for PTSD is exposure therapy, which can be delivered in different formats, e. g. via virtual reality (VR) and as imaginal exposure. The goal of this study is to test the difference between 4 study conditions: virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both combined with an antibiotic drug, DCS (active pill vs. placebo). D-Cycloserine (DCS), a drug that has been FDA approved for over 20 years, has been hypothesized to enhance the therapeutic effects of exposure therapy.). A secondary purpose of this study is to examine predictors for PTSD and response to PTSD intervention in active duty military personnel, veterans, and civilians who served in Iraq/Afghanistan. Psychophysiological factors (e.g. heart rate, blood pressure) and/or a genetic polymorphism (BDNF Val66Met) obtained from a saliva sample will be examined. The two primary co-aims are 1. to examine the effects of DCS versus placebo (PLA) augmentation of exposure therapy on PTSD symptoms, and 2. to examine the relative efficacy of virtual reality enhanced exposure therapy (VRE) and exposure therapy (PE) on PTSD symptoms.
Interventions
DRUGDCS (D-Cycloserine ) + Prolonged Imaginal Exposure
50mg DCS (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure
DRUGDCS (D-Cycloserine ) + Virtual Reality Exposure
50mg DCS (taken once a week on the day of the therapy session) + Virtual Reality Exposure
DRUGPlacebo + Prolonged Imaginal Exposure
Placebo (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure
DRUGPlacebo (sugar pill) + Virtual Reality Exposure
Placebo (taken once a week on the day of the therapy session) + Virtual Reality Exposure
Sponsors
United States Department of Defense
Emory University
University of Southern California
VA Long Beach Healthcare System
National Intrepid Center of Excellence
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
The two primary co-aims of this study are 1. to examine the effects of DCS versus placebo (PLA) augmentation of exposure therapy on PTSD symptoms and 2. to examine the relative efficacy of virtual reality enhanced exposure therapy (VRE) and exposure therapy (PE) on PTSD symptoms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of OEF-OIF (Operations Enduring Freedom or Iraqi Freedom) Combat Related PTSD; 2. Female participants of childbearing potential must agree to use an effective method of birth control (i.e., oral contraceptive, Norplant, diaphragm, condom, or spermicide) during the course of the study, or to remain abstinent from sex, to ensure they do not become pregnant during the course of the study; 3. Ability to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments; 4. Participants must be literate in English; 5. Patients must be medically healthy and willing to take the study drug; 6. VRE stimuli available must be consistent with subject's trauma.
Exclusion criteria
1. Lifetime or current diagnosis of schizophrenia or other psychotic disorder, bipolar disorder; 2. Participation in a clinical trial during the previous 3 months; 3. Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, CNS tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment; 4. Patients who in the investigator's judgment pose a current suicidal or homicidal risk; 5. Alcohol, medication, or illegal substance dependence within the past 90 days; 6. Treatment with any other concomitant medication with primarily CNS activity, or treatment with any medication that the PI judges not acceptable for this study; 7. history of seizures; 8. Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CAPS-IV at the End of Treatment | after weekly treatment session 9 (at posttreatment assessment) | Clinician Administered PTSD Scale (CAPS) for the DSM-IV \[34\]. The CAPS-IV is a structured clinical interview designed to assess the 17 DSM-IV PTSD symptoms. CAPS-IV provides categorical ratings of diagnostic status as well as a quantitative index of symptom severity. The CAPS total severity score is based on response to the 17 items that assess the frequency and intensity of current PTSD symptoms. Symptom severity is assessed separately for past month and past week time frames. CAPS-IV range is 0-136, higher scores mean a worse outcome. |
Countries
United States
Participant flow
Pre-assignment details
Total sample size is n=192. Randomization allocation ratio was 1:1:1:1 to VRE vs. PE and DCS vs. placebo. Study had 2 co-primary aims to examine: 1. the effects of DCS (n=95) vs placebo (n=97) augmentation of exposure therapy 2. the relative efficacy of VRE (n=97) and PE (n=95) on PTSD symptoms.
Participants by arm
| Arm | Count |
|---|---|
| Virtual Reality Exposure (VRE)+Drug: DCycloserine (DCS) Virtual Reality Exposure (VRE): PTSD treatment + D-Cycloserine (DCS) (taken once a week on the day of the therapy session) | 47 |
| Prolonged Imaginal Exposure (PE)+Drug: DCycloserine (DCS) Prolonged Imaginal Exposure (PE): PTSD treatment + D-Cycloserine (DCS) (taken once a week on the day of the therapy session) | 48 |
| Virtual Reality Exposure (VRE)+Drug: Placebo Virtual Reality Exposure (VRE): PTSD treatment + Placebo (sugar pill) (taken once a week on the day of the therapy session) | 50 |
| Prolonged Imaginal Exposure (PE)+Drug: Placebo Prolonged Imaginal Exposure (PE): PTSD treatment + Placebo (sugar pill) (taken once a week on the day of the therapy session) | 47 |
| Total | 192 |
Baseline characteristics
| Characteristic | Total | Virtual Reality Exposure (VRE)+Drug: DCycloserine (DCS) | Prolonged Imaginal Exposure (PE)+Drug: DCycloserine (DCS) | Virtual Reality Exposure (VRE)+Drug: Placebo | Prolonged Imaginal Exposure (PE)+Drug: Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 34.62 years STANDARD_DEVIATION 7.8 | 33.74 years STANDARD_DEVIATION 7.69 | 36.17 years STANDARD_DEVIATION 8.53 | 34.80 years STANDARD_DEVIATION 6.99 | 33.70 years STANDARD_DEVIATION 7.95 |
| CAPS-IV, past week | 73.04 units on a scale STANDARD_DEVIATION 19.47 | 71.72 units on a scale STANDARD_DEVIATION 19.98 | 75.08 units on a scale STANDARD_DEVIATION 18.69 | 74.46 units on a scale STANDARD_DEVIATION 19.11 | 70.74 units on a scale STANDARD_DEVIATION 200.37 |
| Race/Ethnicity, Customized African American/Black | 29 Participants | 8 Participants | 6 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 53 Participants | 16 Participants | 14 Participants | 10 Participants | 13 Participants |
| Race/Ethnicity, Customized Other | 22 Participants | 3 Participants | 7 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 88 Participants | 20 Participants | 21 Participants | 26 Participants | 21 Participants |
| Sex: Female, Male Female | 20 Participants | 6 Participants | 6 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 172 Participants | 41 Participants | 42 Participants | 47 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 97 | 0 / 95 | 0 / 95 | 0 / 97 |
| other Total, other adverse events | 0 / 97 | 0 / 95 | 0 / 95 | 0 / 97 |
| serious Total, serious adverse events | 0 / 97 | 3 / 95 | 0 / 95 | 1 / 97 |
Outcome results
Primary
CAPS-IV at the End of Treatment
Clinician Administered PTSD Scale (CAPS) for the DSM-IV \[34\]. The CAPS-IV is a structured clinical interview designed to assess the 17 DSM-IV PTSD symptoms. CAPS-IV provides categorical ratings of diagnostic status as well as a quantitative index of symptom severity. The CAPS total severity score is based on response to the 17 items that assess the frequency and intensity of current PTSD symptoms. Symptom severity is assessed separately for past month and past week time frames. CAPS-IV range is 0-136, higher scores mean a worse outcome.
Time frame: after weekly treatment session 9 (at posttreatment assessment)
Population: Total sample size is n=192. Randomization allocation ratio was 1:1:1:1 to VRE vs. PE and DCS vs. placebo.~Study had 2 co-primary aims to examine:~1. the effects of DCS (n=95) vs placebo (n=97) augmentation of exposure therapy~2. the relative efficacy of VRE (n=97) and PE (n=95) on PTSD symptoms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Virtual Reality Exposure (VRE) | CAPS-IV at the End of Treatment | 52.42 units on a scale | Standard Deviation 26.55 |
| Prolonged Imaginal Exposure (PE) | CAPS-IV at the End of Treatment | 50.61 units on a scale | Standard Deviation 25.22 |
| Drug: D-Cycloserine (DCS) | CAPS-IV at the End of Treatment | 54.20 units on a scale | Standard Deviation 26.72 |
| Drug: Placebo | CAPS-IV at the End of Treatment | 48.59 units on a scale | Standard Deviation 24.71 |